The overall aim of this research is to investigate a spontaneously occurring animal model of airway obstruction and hyperreactivity two feature of human asthma. Horses and ponies develop recurrent airway obstruction and hyperreactivity to antigens, aerosol and intravenous histamine. This proposal will investigate autonomic mechanism and changes in the permeability of airway epithelium as potential mechanisms of the airway obstruction and hyperreactivity observed in ponies. Reactivity will be measured be determining changes in pulmonary resistance and dynamic compliance induced by increading doses of either histamine, citric acid, or methacholine. The role of the parasympathetic nervous system will be investigated by determining lung function and reactivity before an after muscarinic blockade with atropine. Beta adrenergic mechanisms will be determined by measuring lung function and reactivity before and after both beta blockade and beta agonist. Alpha-adrenergic involvement will be evaluated by determining dose response of airways to an alpha adrenergic agonist before and after muscarinic and beta-adrenergic blockade and by use of specific alpha1 and alpha2 antagonists. Airway epithelial permeability will be investigated using intratracheal injections of mannitol. All studies will be conducted during acute airway obstruction and during clinical remission.